Dynamic Gel Improves Organoid Growth for Reliable Lab Studies

Scientists are refining the process of growing miniature organs in the lab, a field known as organoid research, with a new material that allows for more predictable and complex development. These lab-grown organoids hold immense promise for studying disease and, potentially, creating replacement tissues, but a longstanding challenge has been their inconsistent growth patterns. Researchers at UC San Francisco have developed a novel gel-like substance that addresses this issue, offering a more stable and supportive environment for organoid formation.

Building a More Realistic Scaffold for Growth

The key to this advancement lies in a modified version of Matrigel, a commonly used but often problematic substance in organoid culture. Matrigel, derived from mouse tumors, can be too fluid for precise bioprinting and too rigid once solidified, hindering natural tissue development. The UCSF team tackled this by incorporating microparticles of alginate, a carbohydrate extracted from algae, into the Matrigel. This created a material with a “wet sand-like” consistency, providing both initial structure and the ability to relax and yield as the organoids grow and reshape themselves – a property known as stress relaxation. This innovation, detailed in a study published in Nature Materials on March 10, 2026, could significantly improve the reliability and complexity of organoid models.

“What turned out to matter most was how the material relaxes over time—something we call stress relaxation,” explained Zev Gartner, Ph.D., professor of Pharmaceutical Chemistry at UCSF and senior author of the paper. “It needs to give way at the same pace that tissues are reshaping themselves.”

The Promise of Bioprinting and Precise Cell Placement

This new material isn’t just about providing a better growing environment; it also enables more precise bioprinting. Researchers have long envisioned using 3D printing techniques to arrange cells into specific shapes, mimicking the architecture of real tissues. However, traditional Matrigel’s properties made this difficult. The alginate-enhanced gel allows scientists to deposit stem cells in precise locations within a petri dish before the cells begin to differentiate and organize. This controlled placement is crucial for creating organoids with defined structures and functions.

Austin Graham, Ph.D., a postdoctoral fellow in Gartner’s lab and the first author of the paper, explained the challenge: “Liquid Matrigel is too runny to print into, and once it solidifies, it pushes back too much. We wanted a material that lets us place cells exactly where we want them but still allows them to grow and organize themselves.”

Mimicking Natural Tissue Development

The team’s approach was informed by an understanding of how tissues develop naturally within embryos. During embryonic development, tissues interact with their surroundings, exerting forces and responding to the mechanical properties of the environment. A rigid environment can stifle development, while an overly fluid one can lead to disorganized growth. The new material strikes a balance, providing enough support for initial structure while allowing for the dynamic changes necessary for proper morphogenesis.

Successful Testing Across Multiple Tissue Types

The researchers tested their method with a variety of organoid-forming tissues, including mouse intestinal and salivary gland cells, human vascular cells, and human stem-cell–derived brain cells. The results were promising. Organoids grown in the new material exhibited improved consistency in shape and size, and often displayed more advanced developmental features, such as sprouting buds. Notably, intestinal cells printed in long lines formed tube-like structures capable of transporting fluids, mirroring the functionality of the human intestine. This suggests the potential for creating functional organoids that can mimic the physiological processes of real organs.

The approach emphasizes allowing cells to self-assemble rather than attempting to build tissues from the ground up. As Gartner set it, “We’re not building tissues like Legos. We place cells where they require to be and let their developmental programs assemble the tissue. The goal is to reach a stage where an organ begins to build itself.”

Implications for Regenerative Medicine and Disease Modeling

The development of this dynamic bioprinting material represents a significant step forward in the field of organoid research. More reliable and complex organoids could revolutionize disease modeling, allowing scientists to study the mechanisms of disease in a more accurate and controlled environment. This could accelerate the development of new therapies and personalized medicine approaches. The ability to create functional organoids opens up possibilities for regenerative medicine, potentially leading to the creation of replacement tissues for patients in need. The team’s work builds on previous research exploring MAGIC matrices as freeform bioprinting materials.

Looking Ahead: Refining the Material and Expanding Applications

Further research will focus on optimizing the composition of the alginate-Matrigel mixture to fine-tune its mechanical properties for different tissue types. Researchers will also explore the potential of using this material to create even more complex organoid structures, such as those found in multi-organ systems. The ultimate goal is to develop a platform that can reliably generate functional human tissues for a wide range of applications, from drug screening to transplantation. The team is also investigating how this material interacts with different cell types and growth factors to further enhance organoid development and function.

Publication details: Austin J. Graham et al, Stress-relaxing granular bioprinting materials enable complex and uniform organoid self-organization, Nature Materials (2026). DOI: 10.1038/s41563-026-02519-4

Journal information: Nature Materials